Evidence for dual components in the non-adrenergic non-cholinergic relaxation in the rat gastric fundus: Role of endogenous nitric oxide and vasoactive intestinal polypeptide

doi:10.1016/0165-1838(92)90039-J

Journal of the Autonomic Nervous System

Volume 37, Issue 3, March 1992, Pages 175-186

Journal of the Auton...

https://doi.org/10.1016/0165-1838(92)90039-J Get rights and content

Abstract

The effects of trypsin and arginine analogues, alone or in combination, on half-maximal non-adrenergic, non-cholinergic (NANC) relaxation elicited by different pulse trains of electrical field stimulation were studied in the rat gastric fundus in order to investigate further the relative contribution of peptides and NO. Trypsin (1 μM) partially inhibited electrically-induced NANC relaxation especially when longer pulse trains were used. l-NOARG, l-NAME and l-NMMA, but not d-NOARG or d-NAME (3–300 μM) produced concentration-dependent inhibition of the electrically induced NANC relaxation. l-Arginine (l-Arg), but not d-Arginine (d-Arg) (3.8 μM-3.8 mM) produced a concentration-dependent reversal of the inhibitory effect of l-NOARG IC₅₀ (38 μM). Neither l-NOARG (38 μM) nor l-Arg (380 μM) influence submaximal relaxation induced by VIP (3 μM), isopropylnoradrenaline (10 μM), ATP (10 μM) or sodium nitroprusside (300 μM). Moreover l-NOARG (100 μM) did not influence neurally-induced VIP release. l-NOARG inhibition of NANC relaxation was significant only when short pulse trains were used, while trypsin showed significant inhibition only of relaxation induced by longer pulse trains. These results suggest that the relaxation induced by the activation of the NANC inhibitory neurotransmission of the rat gastric fundus consists of at least two components, one trypsin-sensitive and the other trypsin-resistant, to which VIP and NO contribute, respectively.

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We examined the characteristics of the non-adrenergic non-cholinergic (NANC) nerve induced relaxation and the possible interaction between nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) on the basal tone of the circular muscle of the rat gastric fundus. Electrically induced NANC relaxations were partly inhibited by N^ω-nitro- $l$ -arginine (100 μ M), whereas sodium nitroprusside (SNP; 10 μ M) and VIP (5 nM) induced relaxations were not affected. 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT; 5 μ M) also inhibited the responses to electrical stimuli to a similar extent as N^ω-nitro- $l$ -arginine but not VIP. However, AMT plus N^ω-nitro- $l$ -arginine did not give an additional inhibition above that of each drug alone on NANC relaxations, and dexamethasone (10 μ M) had no effect on NANC nerve induced relaxations. 1H-[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μ M), a selective inhibitor of guanylate cyclase, abolished the responses to NANC nerve stimulation and SNP, while VIP responses were not influenced. N-ethylmaleimide (100μ M), an adenylate cyclase inhibitor, attenuated relaxations to NANC nerve stimulation, VIP and isoproterenol (1 nM), while having no effect on those to SNP, but in combination with N^ω-nitro- $l$ -arginine, there was no additional inhibition on the responses to nerve stimulation. Alpha-chymotrypsin (10 u ml⁻¹) severely diminished VIP induced relaxations, but did not reduce electrical responses. In conclusion, these results suggest that NO is involved in the relaxations induced by short-term electrical stimulation. However, another possible unidentified transmitter that can trigger the accumulation of cyclic GMP is not entirely ruled out and there is no interaction between NO and VIP in the circular muscle strip of the rat gastric fundus, even in the basal state of the tissue.
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In the rat and human, NOS-immunoreactive neuronal cell bodies and fibers have been detected throughout the entire gastrointestinal tract [1,4]. Stimulation of the myenteric plexus releases NO, which in turn produces relaxation of the smooth muscle in the gastrointestinal tract [3,4,6,7]. NO appears to play an important role in mediating descending relaxation in the rat colon, an essential component of the peristaltic reflex [13,14].
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Research paperEvidence for dual components in the non-adrenergic non-cholinergic relaxation in the rat gastric fundus: Role of endogenous nitric oxide and vasoactive intestinal polypeptide

Abstract

Eur. J. Pharmacol.

Neuroscience

Biochem. Biophys. Res. Commun.

Eur. J. Pharmacol.

Non-adrenergic non-cholinergic nervous control of gastrointestinal motility patterns

Arch. Int. Pharmacodyn.

Acetylcholine induces vasodilatation in the rabbit isolated heart through the release of nitric oxide, the endogenous nitrovasodilator

Br. J. Pharmacol.

Motor activity and neurotransmitter release in the gastric fundus of streptozotocin-diabetic rats

Eur. J. Pharmacol.

Release of nitric oxide upon stimulation of nonadrenergic noncholinergic nerves in the rat gastric fundus

J. Pharm. Exp. Ther.

Localization of nitric oxide synthase indicating a neural role for nitric oxide

Nature

Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter

Nature

Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic non-cholinergic (purinergic) inhibitory nerves

Br. J. Pharmacol.

Is peptide histidine isoleucine an inhibitory nonadrenergic non-cholinergic neurotransmitter in the rat gastric fundus?

Arch. Int. Pharmacodyn.

Effects of nitric oxide synthase inhibitors on the relaxation induced by non-adrenergic non-cholinergic nerve-stimulation in the rat gastric fundus

Pharm. Res.

l-NG-nitro arginine partially inhibits non-adrenergic non-cholinergic relaxation in the rat gastric fundus

Gastroenterology

Influence of chymotrypsin and trypsin on the non-adrenergic noncholinergic relaxation in the rat gastric fundus

Br. J. Pharmacol.

Vasoactive intestinal polypeptide as possible mediator of non-adrenergic non-cholinergic relaxation in the rat gastric fundus

J. Pharm. Pharmacol.

Research paper
Evidence for dual components in the non-adrenergic non-cholinergic relaxation in the rat gastric fundus: Role of endogenous nitric oxide and vasoactive intestinal polypeptide

l-N^G-nitro arginine partially inhibits non-adrenergic non-cholinergic relaxation in the rat gastric fundus